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  1. Zhou C, Tang KJ, Cho BC, Liu B, Paz-Ares L, Cheng S, et al.
    N Engl J Med, 2023 Nov 30;389(22):2039-2051.
    PMID: 37870976 DOI: 10.1056/NEJMoa2306441
    BACKGROUND: Amivantamab has been approved for the treatment of patients with advanced non-small-cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) exon 20 insertions who have had disease progression during or after platinum-based chemotherapy. Phase 1 data showed the safety and antitumor activity of amivantamab plus carboplatin-pemetrexed (chemotherapy). Additional data on this combination therapy are needed.

    METHODS: In this phase 3, international, randomized trial, we assigned in a 1:1 ratio patients with advanced NSCLC with EGFR exon 20 insertions who had not received previous systemic therapy to receive intravenous amivantamab plus chemotherapy (amivantamab-chemotherapy) or chemotherapy alone. The primary outcome was progression-free survival according to blinded independent central review. Patients in the chemotherapy group who had disease progression were allowed to cross over to receive amivantamab monotherapy.

    RESULTS: A total of 308 patients underwent randomization (153 to receive amivantamab-chemotherapy and 155 to receive chemotherapy alone). Progression-free survival was significantly longer in the amivantamab-chemotherapy group than in the chemotherapy group (median, 11.4 months and 6.7 months, respectively; hazard ratio for disease progression or death, 0.40; 95% confidence interval [CI], 0.30 to 0.53; P<0.001). At 18 months, progression-free survival was reported in 31% of the patients in the amivantamab-chemotherapy group and in 3% in the chemotherapy group; a complete or partial response at data cutoff was reported in 73% and 47%, respectively (rate ratio, 1.50; 95% CI, 1.32 to 1.68; P<0.001). In the interim overall survival analysis (33% maturity), the hazard ratio for death for amivantamab-chemotherapy as compared with chemotherapy was 0.67 (95% CI, 0.42 to 1.09; P = 0.11). The predominant adverse events associated with amivantamab-chemotherapy were reversible hematologic and EGFR-related toxic effects; 7% of patients discontinued amivantamab owing to adverse reactions.

    CONCLUSIONS: The use of amivantamab-chemotherapy resulted in superior efficacy as compared with chemotherapy alone as first-line treatment of patients with advanced NSCLC with EGFR exon 20 insertions. (Funded by Janssen Research and Development; PAPILLON ClinicalTrials.gov number, NCT04538664.).

    Matched MeSH terms: Pemetrexed/administration & dosage; Carboplatin/administration & dosage
  2. Kew CH, Ahmad Basir KF, Low DW, Loh KC
    Med J Malaysia, 2023 Jul;78(4):437-444.
    PMID: 37518909
    INTRODUCTION: Topical corticosteroid phobia is a common phenomenon that can result in poor treatment adherence and therapeutic failure.

    OBJECTIVES: This study aims to evaluate the prevalence and degree of topical corticosteroid phobia and its impact on treatment adherence in various dermatological conditions. Additionally, we explored the sources of information regarding topical corticosteroids.

    MATERIALS AND METHODS: A cross-sectional study was conducted among 300 participants with topical corticosteroid usage experience. Topical corticosteroid phobia was assessed with the topical corticosteroid phobia (TOPICOP) scale, and treatment adherence was measured with the Elaboration d'un outil d'evaluation de l'observance des traitements medicamenteux (ECOB) score. Information sources regarding topical corticosteroids were identified, and their level of trust was assessed. The data were collected via questionnaires in three languages, namely English, Malay and Mandarin.

    RESULTS: The study found that topical corticosteroid phobia was prevalent, with 98% of participants expressing a certain degree of phobia. The mean global TOPICOP score was 32.7 ± 6.7%. The mean score of each domain was 27.1 ± 17.2% for knowledge and belief, 35.7 ± 23.8% for fears and 40.8 ± 25.8% for behaviour. Patients/caregivers who have eczema, highly educated, severe disease, low tolerability to symptoms, previous adverse effects with topical corticosteroids and tend to traditional/non-steroidal alternative therapy usage had a significant association with topical corticosteroid phobia (p<0.05). Dermatologists were the most common and trusted source of information on topical corticosteroids.

    CONCLUSIONS: This study highlights the widespread topical corticosteroid phobia in dermatological practice. Dermatologists should take the lead in combating steroid phobia and provide patients with public awareness regarding topical corticosteroids to improve treatment adherence and therapeutic outcomes.

    Matched MeSH terms: Adrenal Cortex Hormones/administration & dosage
  3. Farooq A, Bilgrami A, Faraz SA, Qazi FUR, Maqsood A, Altamash S, et al.
    J Appl Biomater Funct Mater, 2023;21:22808000231166210.
    PMID: 37029505 DOI: 10.1177/22808000231166210
    OBJECTIVES: This study aimed to compare the effectiveness of an experimental root canal irrigant and 17% Ethylene-di-amine tetra acetic acid for removal of the smear layer in the coronal, middle and apical portions of the root canal.

    MATERIALS AND METHODS: Ninety human single rooted maxillary and mandibular teeth were selected for this study. The teeth were randomly divided into two experimental groups and one control group as follows: Group A (Ethanolic extract of Sapindus Mukorossi), Group B (17% EDTA), and Group C (Distilled water). The root canals of all three groups were prepared with stainless steel K-files by means of the standard step-back technique and irrigated with 5.25% sodium hypo chloride. The teeth were decoronated, following the irrigation and divided longitudinally into two-halves and visualized using scanning electron microscope (SEM) for the amount of smear layer present utilizing the three-point score system. The observations were noted both before and after the treatment. Nonparametric tests were applied for the comparison and p-value ⩽ 0.05 was considered as statistically significant.

    RESULTS: It was evident from that smear layer was completely removed in coronal portion of 27 out of 30 teeth in-group A. For middle and apical areas of group A, 24 and 19 teeth showed complete smear layer removal. In-group B it was found that there were 24, 21, and 3 teeth at coronal, middle and apical, areas respectively where smear layer were completely absent. Intra group comparison showed a significant difference (p = 0.002) in smear layer removal was found for group A at coronal, middle and apical thirds. Similarly, a significant difference (p = 0.001) was also found for group B; however heavy smear layer was found among the three parts of the canal for group C.

    CONCLUSIONS: Ethanolic extract of Sapindus Mukorossi have higher effectiveness in removing the smear layer from the root canal in comparison to 17% EDTA.

    Matched MeSH terms: Plant Extracts/administration & dosage
  4. Gao Q, Zhu J, Zhao W, Huang Y, An R, Zheng H, et al.
    Clin Cancer Res, 2022 Jun 01;28(11):2278-2285.
    PMID: 35131903 DOI: 10.1158/1078-0432.CCR-21-3023
    PURPOSE: In patients with platinum-sensitive relapsed (PSR) ovarian cancer, olaparib maintenance monotherapy significantly improves progression-free survival (PFS) versus placebo. However, evidence in the Asian population is lacking. This is the first study to evaluate olaparib efficacy and tolerability exclusively in Asian patients with PSR ovarian cancer.

    PATIENTS AND METHODS: Considering the limited placebo effect and significant clinical benefit of olaparib in previous trials, and the rapid approval of olaparib in China, this phase III study was designed as an open-label, single-arm trial. Patients with high-grade epithelial PSR ovarian cancer were enrolled from country-wide clinical centers across China and Malaysia. Patients received oral olaparib (300 mg) twice daily until disease progression or unacceptable toxicity. Primary endpoint was median PFS (mPFS). Primary analysis of PFS using the Kaplan-Meier method was performed when data reached 60% maturity (clinicaltrials.gov NCT03534453).

    RESULTS: Between 2018 and 2020, 225 patients were enrolled, and 224 received olaparib; 35.7% had received ≥3 lines of chemotherapy, 35.3% had achieved complete response to their last line of platinum-based chemotherapy, and 41.1% had a platinum-free interval ≤12 months. At primary data cut-off (December 25, 2020), overall mPFS was 16.1 months; mPFS was 21.2 and 11.0 months in BRCA-mutated and wild-type BRCA subgroups, respectively. Adverse events (AE) occurred in 99.1% of patients (grade ≥3, 48.7%); 9.4% discontinued therapy due to treatment-related AEs.

    CONCLUSIONS: Olaparib maintenance therapy was highly effective and well tolerated in Asian patients with PSR ovarian cancer, regardless of BRCA status. This study highlights the promising efficacy of olaparib in this Asian population. See related commentary by Nicum and Blagden, p. 2201.

    Matched MeSH terms: Phthalazines/administration & dosage; Piperazines/administration & dosage
  5. WHO Solidarity Trial Consortium
    Lancet, 2022 May 21;399(10339):1941-1953.
    PMID: 35512728 DOI: 10.1016/S0140-6736(22)00519-0
    BACKGROUND: The Solidarity trial among COVID-19 inpatients has previously reported interim mortality analyses for four repurposed antiviral drugs. Lopinavir, hydroxychloroquine, and interferon (IFN)-β1a were discontinued for futility but randomisation to remdesivir continued. Here, we report the final results of Solidarity and meta-analyses of mortality in all relevant trials to date.

    METHODS: Solidarity enrolled consenting adults (aged ≥18 years) recently hospitalised with, in the view of their doctor, definite COVID-19 and no contraindication to any of the study drugs, regardless of any other patient characteristics. Participants were randomly allocated, in equal proportions between the locally available options, to receive whichever of the four study drugs (lopinavir, hydroxychloroquine, IFN-β1a, or remdesivir) were locally available at that time or no study drug (controls). All patients also received the local standard of care. No placebos were given. The protocol-specified primary endpoint was in-hospital mortality, subdivided by disease severity. Secondary endpoints were progression to ventilation if not already ventilated, and time-to-discharge from hospital. Final log-rank and Kaplan-Meier analyses are presented for remdesivir, and are appended for all four study drugs. Meta-analyses give weighted averages of the mortality findings in this and all other randomised trials of these drugs among hospital inpatients. Solidarity is registered with ISRCTN, ISRCTN83971151, and ClinicalTrials.gov, NCT04315948.

    FINDINGS: Between March 22, 2020, and Jan 29, 2021, 14 304 potentially eligible patients were recruited from 454 hospitals in 35 countries in all six WHO regions. After the exclusion of 83 (0·6%) patients with a refuted COVID-19 diagnosis or encrypted consent not entered into the database, Solidarity enrolled 14 221 patients, including 8275 randomly allocated (1:1) either to remdesivir (ten daily infusions, unless discharged earlier) or to its control (allocated no study drug although remdesivir was locally available). Compliance was high in both groups. Overall, 602 (14·5%) of 4146 patients assigned to remdesivir died versus 643 (15·6%) of 4129 assigned to control (mortality rate ratio [RR] 0·91 [95% CI 0·82-1·02], p=0·12). Of those already ventilated, 151 (42·1%) of 359 assigned to remdesivir died versus 134 (38·6%) of 347 assigned to control (RR 1·13 [0·89-1·42], p=0·32). Of those not ventilated but on oxygen, 14·6% assigned to remdesivir died versus 16·3% assigned to control (RR 0·87 [0·76-0·99], p=0·03). Of 1730 not on oxygen initially, 2·9% assigned to remdesivir died versus 3·8% assigned to control (RR 0·76 [0·46-1·28], p=0·30). Combining all those not ventilated initially, 11·9% assigned to remdesivir died versus 13·5% assigned to control (RR 0·86 [0·76-0·98], p=0·02) and 14·1% versus 15·7% progressed to ventilation (RR 0·88 [0·77-1·00], p=0·04). The non-prespecified composite outcome of death or progression to ventilation occurred in 19·6% assigned to remdesivir versus 22·5% assigned to control (RR 0·84 [0·75-0·93], p=0·001). Allocation to daily remdesivir infusions (vs open-label control) delayed discharge by about 1 day during the 10-day treatment period. A meta-analysis of mortality in all randomised trials of remdesivir versus no remdesivir yielded similar findings.

    INTERPRETATION: Remdesivir has no significant effect on patients with COVID-19 who are already being ventilated. Among other hospitalised patients, it has a small effect against death or progression to ventilation (or both).

    FUNDING: WHO.

    Matched MeSH terms: Oxygen/administration & dosage
  6. Leeyaphan C, Varothai S, Trakanwittayarak S, Suphatsathienkul P, Pattaravadee S, Matthapan L, et al.
    J Cosmet Dermatol, 2022 Feb;21(2):679-688.
    PMID: 33811776 DOI: 10.1111/jocd.14125
    BACKGROUND: Intertrigo is an inflammatory skin-fold condition. Candida infections may occur concurrently or afterward. Topical corticosteroids may reduce inflammation but exacerbate Candida infections. The treatment is contentious.

    OBJECTIVE: To evaluate the efficacies and safety of adsorbent lotion containing tapioca starch, spent grain wax, Butyrospermum parkii extract, argania spinosa kernel oil, aloe barbadensis, rosehip oil, and allantoin for the treatment of mild-to-moderate intertrigo, relative to 1% hydrocortisone cream.

    METHODS: This randomized, double-blinded study enrolled 40 intertrigo patients. Twice daily, 20 patients applied adsorbent lotion while the remainder used 1% hydrocortisone cream. Efficacy evaluation, skin biophysical measurements, skin tolerability, safety, and visual analog scale (VAS) patient-satisfaction scores were evaluated at baseline and Week 2.

    RESULTS: The adsorbent lotion showed higher complete cure rates for color, partial epidermal loss, papules/pustules/vesicles/patches, dryness, and scaling than the corticosteroid without statistical significance. Adsorbent lotion demonstrated significantly higher reduction in pruritus than the corticosteroid treatment. Reduction of erythema level using Mexameter and VAS patient-satisfaction scores were not statistically different between adsorbent lotion and hydrocortisone cream. No adverse effects or superimposed infections were reported.

    CONCLUSIONS: The anti-inflammatory efficacies of adsorbent lotion and low-potency steroid were equivalent. The lotion was safe and produced excellent pruritus reduction. Patient satisfaction was high.

    Matched MeSH terms: Adrenal Cortex Hormones/administration & dosage
  7. Chalhoub NE, Wenderfer SE, Levy DM, Rouster-Stevens K, Aggarwal A, Savani SI, et al.
    Arthritis Rheumatol, 2022 Feb;74(2):263-273.
    PMID: 34279063 DOI: 10.1002/art.41930
    OBJECTIVE: To develop a standardized steroid dosing regimen (SSR) for physicians treating childhood-onset systemic lupus erythematosus (SLE) complicated by lupus nephritis (LN), using consensus formation methodology.

    METHODS: Parameters influencing corticosteroid (CS) dosing were identified (step 1). Data from children with proliferative LN were used to generate patient profiles (step 2). Physicians rated changes in renal and extrarenal childhood-onset SLE activity between 2 consecutive visits and proposed CS dosing (step 3). The SSR was developed using patient profile ratings (step 4), with refinements achieved in a physician focus group (step 5). A second type of patient profile describing the course of childhood-onset SLE for ≥4 months since kidney biopsy was rated to validate the SSR-recommended oral and intravenous (IV) CS dosages (step 6). Patient profile adjudication was based on majority ratings for both renal and extrarenal disease courses, and consensus level was set at 80%.

    RESULTS: Degree of proteinuria, estimated glomerular filtration rate, changes in renal and extrarenal disease activity, and time since kidney biopsy influenced CS dosing (steps 1 and 2). Considering these parameters in 5,056 patient profile ratings from 103 raters, and renal and extrarenal course definitions, CS dosing rules of the SSR were developed (steps 3-5). Validation of the SSR for up to 6 months post-kidney biopsy was achieved with 1,838 patient profile ratings from 60 raters who achieved consensus for oral and IV CS dosage in accordance with the SSR (step 6).

    CONCLUSION: The SSR represents an international consensus on CS dosing for use in patients with childhood-onset SLE and proliferative LN. The SSR is anticipated to be used for clinical care and to standardize CS dosage during clinical trials.

    Matched MeSH terms: Glucocorticoids/administration & dosage*
  8. Azfaralariff A, Farahfaiqah F, Shahid M, Sanusi SA, Law D, Mohd Isa AR, et al.
    J Ethnopharmacol, 2022 Jan 30;283:114751.
    PMID: 34662662 DOI: 10.1016/j.jep.2021.114751
    ETHNOPHARMACOLOGICAL RELEVANCE: Marantodes pumilum (MP) herbs, locally known as Kacip Fatimah, are widely used traditionally to improve women's health. The herb is frequently used for gynecological issues such as menstrual problems, facilitating and quickening delivery, post-partum medication, treats flatulence and dysentery, and. MP extracts are thought to aid in the firming and toning of abdominal muscles, tighten breasts and vaginal muscles, and anti-dysmenorrhea. It also was used for the treatment of gonorrhea and hemorrhoids. As MP product has been produced commercially recently, more in-depth studies should be conducted. The presence of numerous active compounds in MP might provide a synergistic effect and potentially offer other health benefits than those already identified and known.

    AIM OF THE STUDY: This study aimed to use a computational target fishing approach to predict the possible therapeutic effect of Marantodes pumilum and evaluated their effectivity.

    MATERIALS AND METHODS: This study involves a computational approach to identify the potential targets by using target fishing. Several databases were used: PubChem database to obtain the chemical structure of interested compounds; Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP) server and the SWISSADME web tool to identify and select the compounds having drug-likeness properties; PharmMapper was used to identify top ten target protein of the selected compounds and Online Mendelian Inheritance in Man (OMIM) was used to predict human genetic problems; the gene id of top-10 proteins was obtained from UniProtKB to be analyzed by using GeneMANIA server to check the genes' function and their co-expression; Gene Pathway established by Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) of the selected targets were analyzed by using EnrichR server and confirmed by using DAVID (The Database for Annotation, Visualization and Integrated Discovery) version 6.8 and STRING database. All the interaction data was analyzed by Cytoscape version 3.7.2 software. The protein structure of most putative proteins was obtained from the RCSB protein data bank. Thedocking analysis was conducted using PyRx biological software v0.8 and illustrated by BIOVIA Discovery Studio Visualizer version 20.1.0. As a preliminary evaluation, a cell viability assay using Sulforhodamine B was conducted to evaluate the potential of the predicted therapeutic effect.

    RESULTS: It was found that four studied compounds are highly correlated with three proteins: EFGR, CDK2, and ESR1. These proteins are highly associated with cancer pathways, especially breast cancer and prostate cancer. Qualitatively, cell proliferation assay conducted shown that the extract has IC50 of 88.69 μg/ml against MCF-7 and 66.51 μg/ml against MDA-MB-231.

    CONCLUSIONS: Natural herbs are one of the most common forms of complementary and alternative medicine, and they play an important role in disease treatment. The results of this study show that in addition to being used traditionally to maintain women's health, the use of Marantodes pumilum indirectly has the potential to protect against the development of cancer cells, especially breast cancer. Therefore, further research is necessary to confirm the potential of this plant to be used in the development of anti-cancer drugs, especially for breast cancer.

    Matched MeSH terms: Antineoplastic Agents, Phytogenic/administration & dosage; Drugs, Chinese Herbal/administration & dosage; Plant Extracts/administration & dosage
  9. Chellappan DK, Prasher P, Saravanan V, Vern Yee VS, Wen Chi WC, Wong JW, et al.
    Chem Biol Interact, 2022 Jan 05;351:109706.
    PMID: 34662570 DOI: 10.1016/j.cbi.2021.109706
    The challenges and difficulties associated with conventional drug delivery systems have led to the emergence of novel, advanced targeted drug delivery systems. Therapeutic drug delivery of proteins and peptides to the lungs is complicated owing to the large size and polar characteristics of the latter. Nevertheless, the pulmonary route has attracted great interest today among formulation scientists, as it has evolved into one of the important targeted drug delivery platforms for the delivery of peptides, and related compounds effectively to the lungs, primarily for the management and treatment of chronic lung diseases. In this review, we have discussed and summarized the current scenario and recent developments in targeted delivery of proteins and peptide-based drugs to the lungs. Moreover, we have also highlighted the advantages of pulmonary drug delivery over conventional drug delivery approaches for peptide-based drugs, in terms of efficacy, retention time and other important pharmacokinetic parameters. The review also highlights the future perspectives and the impact of targeted drug delivery on peptide-based drugs in the coming decade.
    Matched MeSH terms: Drug Carriers/administration & dosage; Peptides/administration & dosage*; Proteins/administration & dosage*; Nanoparticles/administration & dosage
  10. Yii RSL, Chuah KH, Poh KS, Lau PC, Ng KL, Ho SH, et al.
    Dig Dis Sci, 2022 01;67(1):344-347.
    PMID: 33491164 DOI: 10.1007/s10620-021-06835-4
    Matched MeSH terms: Minerals/administration & dosage
  11. Ramatillah DL, Gan SH, Pratiwy I, Syed Sulaiman SA, Jaber AAS, Jusnita N, et al.
    PLoS One, 2022;17(1):e0262438.
    PMID: 35077495 DOI: 10.1371/journal.pone.0262438
    BACKGROUND AND AIM: Coronavirus Disease 2019 (COVID-19) has become a worldwide pandemic and is a threat to global health. Patients who experienced cytokine storms tend to have a high mortality rate. However, to date, no study has investigated the impact of cytokine storms.

    MATERIALS AND METHODS: This retrospective cohort study included only COVID-19 positive patients hospitalized in a Private Hospital in West Jakarta between March and September 2020. All patients were not vaccinated during this period and treatment was based on the guidelines by the Ministry of Health Indonesia. A convenience sampling method was used and all patients who met the inclusion criteria were enrolled.

    RESULTS: The clinical outcome of COVID-19 patients following medical therapy was either cured (85.7%) or died (14.3%), with 14.3% patients reported to have cytokine storm, from which 23.1% led to fatalities. A plasma immunoglobulin (Gammaraas®) and/or tocilizumab (interleukin-6 receptor antagonist; Actemra®) injection was utilised to treat the cytokine storm while remdesivir and oseltamivir were administered to ameliorate COVID-19. Most (61.5%) patients who experienced the cytokine storm were male; mean age 60 years. Interestingly, all patients who experienced the cytokine storm had hypertension or/ and diabetes complication (100%). Fever, cough and shortness of breath were also the common symptoms (100.0%). Almost all (92.3%) patients with cytokine storm had to be treated in the intensive care unit (ICU). Most (76.9%) patients who had cytokine storm received hydroxychloroquine and all had antibiotics [1) azithromycin + levofloxacin or 2) meropenam for critically ill patients] and vitamins such as vitamins C and B-complex as well as mineral. Unfortunately, from this group, 23.1% patients died while the remaining 70% of patients recovered. A significant (p<0.05) correlation was established between cytokine storms and age, the presence of comorbidity, diabetes, hypertension, fever, shortness of breath, having oxygen saturation (SPO2) less than 93%, cold, fatigue, ward of admission, the severity of COVID-19 disease, duration of treatment as well as the use of remdesivir, Actemra® and Gammaraas®. Most patients recovered after receiving a combination treatment (oseltamivir + remdesivir + Antibiotics + Vitamin/Mineral) for approximately 11 days with a 90% survival rate. On the contrary, patients who received oseltamivir + hydroxychloroquine + Gammaraas® + antibiotics +Vitamin/Mineral, had a 83% survival rate after being admitted to the hospital for about ten days.

    CONCLUSION: Factors influencing the development of a cytokine storm include age, duration of treatment, comorbidity, symptoms, type of admission ward and severity of infection. Most patients (76.92%) with cytokine storm who received Gammaraas®/Actemra®, survived although they were in the severe and critical levels (87.17%). Overall, based on the treatment duration and survival rate, the most effective therapy was a combination of oseltamivir + favipiravir + hydroxychloroquine + antibiotics + vitamins/minerals.

    Matched MeSH terms: Adenosine Monophosphate/administration & dosage; Alanine/administration & dosage; Anti-Bacterial Agents/administration & dosage; Vitamins/administration & dosage; Antibodies, Monoclonal, Humanized/administration & dosage
  12. Muhammad Sakri MS, Tengku Din TADA, Jaafar H, Gopalan V, Wan Abdul Rahman WF
    Int J Immunopathol Pharmacol, 2022;36:20587384211059673.
    PMID: 35037503 DOI: 10.1177/20587384211059673
    Angiogenesis is the process of new vascular formation, which is derived from various factors. For suppressing cancer cell growth, targeting angiogenesis is one of the therapeutic approaches. Vascular endothelial growth factor family receptors, including Flt-1, Flk-1 and Flt-4, have been found to play an essential role in regulating angiogenesis. Rapamycin is a macrolide compound with anti-proliferative properties, while platelet factor-4 (PF-4) is an antiangiogenic ELR-negative chemokine. Rapamycin inhibits mTOR ligands activation, thus suppressing cell proliferation, while PF-4 inhibits cell proliferation through several mechanisms. In the present study, we evaluated the effects of rapamycin and platelet factor-4 toward breast carcinoma at the proteomic and genomic levels. A total of 60 N-Methyl-N-Nitrosourea-induced rat breast carcinomas were treated with rapamycin, platelet factor-4 and rapamycin+platelet factor-4. The tumours were subsequently subjected to immunohistochemical protein analysis and polymerase chain reaction gene analysis. Protein analysis was performed using a semiquantitative scoring method, while the mRNA expression levels were analysed based on the relative expression ratio. There was a significant difference in the protein and mRNA expression levels for the selected markers. In the rapamycin+platelet factor-4-treated group, the Flt-4 marker was downregulated, whereas there were no differences in the expression levels of other markers, such as Flt-1 and Flk-1. On the other hand, platelet factor-4 did not exhibit a superior angiogenic inhibiting ability in this study. Rapamycin is a potent antiangiogenic drug; however, platelet factor-4 proved to be a less effective drug of anti-angiogenesis on rat breast carcinoma model.
    Matched MeSH terms: Platelet Factor 4/administration & dosage*; Sirolimus/administration & dosage*; Angiogenesis Inhibitors/administration & dosage*
  13. Bachelez H, Choon SE, Marrakchi S, Burden AD, Tsai TF, Morita A, et al.
    N Engl J Med, 2021 12 23;385(26):2431-2440.
    PMID: 34936739 DOI: 10.1056/NEJMoa2111563
    BACKGROUND: Generalized pustular psoriasis (GPP) is a rare, life-threatening, inflammatory skin disease characterized by widespread eruption of sterile pustules. Interleukin-36 signaling is involved in the pathogenesis of this disorder. Spesolimab, a humanized anti-interleukin-36 receptor monoclonal antibody, is being studied for the treatment of GPP flares.

    METHODS: In a phase 2 trial, we randomly assigned patients with a GPP flare in a 2:1 ratio to receive a single 900-mg intravenous dose of spesolimab or placebo. Patients in both groups could receive an open-label dose of spesolimab on day 8, an open-label dose of spesolimab as a rescue medication after day 8, or both and were followed to week 12. The primary end point was a Generalized Pustular Psoriasis Physician Global Assessment (GPPGA) pustulation subscore of 0 (range, 0 [no visible pustules] to 4 [severe pustulation]) at the end of week 1. The key secondary end point was a GPPGA total score of 0 or 1 (clear or almost clear skin) at the end of week 1; scores range from 0 to 4, with higher scores indicating greater disease severity.

    RESULTS: A total of 53 patients were enrolled: 35 were assigned to receive spesolimab and 18 to receive placebo. At baseline, 46% of the patients in the spesolimab group and 39% of those in the placebo group had a GPPGA pustulation subscore of 3, and 37% and 33%, respectively, had a pustulation subscore of 4. At the end of week 1, a total of 19 of 35 patients (54%) in the spesolimab group had a pustulation subscore of 0, as compared with 1 of 18 patients (6%) in the placebo group (difference, 49 percentage points; 95% confidence interval [CI], 21 to 67; P<0.001). A total of 15 of 35 patients (43%) had a GPPGA total score of 0 or 1, as compared with 2 of 18 patients (11%) in the placebo group (difference, 32 percentage points; 95% CI, 2 to 53; P = 0.02). Drug reactions were reported in 2 patients who received spesolimab, in 1 of them concurrently with a drug-induced hepatic injury. Among patients assigned to the spesolimab group, infections occurred in 6 of 35 (17%) through the first week; among patients who received spesolimab at any time in the trial, infections had occurred in 24 of 51 (47%) at week 12. Antidrug antibodies were detected in 23 of 50 patients (46%) who received at least one dose of spesolimab.

    CONCLUSIONS: In a phase 2 randomized trial involving patients with GPP, the interleukin-36 receptor inhibitor spesolimab resulted in a higher incidence of lesion clearance at 1 week than placebo but was associated with infections and systemic drug reactions. Longer and larger trials are warranted to determine the effect and risks of spesolimab in patients with pustular psoriasis. (Funded by Boehringer Ingelheim; Effisayil 1 ClinicalTrials.gov number, NCT03782792.).

    Matched MeSH terms: Antibodies, Monoclonal, Humanized/administration & dosage
  14. Naomi R, Embong H, Othman F, Ghazi HF, Maruthey N, Bahari H
    Nutrients, 2021 Dec 22;14(1).
    PMID: 35010895 DOI: 10.3390/nu14010020
    Alzheimer's disease (AD) is the most common form of neurodegenerative disorders affecting mostly the elderly. It is characterized by the presence of Aβ and neurofibrillary tangles (NFT), resulting in cognitive and memory impairment. Research shows that alteration in gut microbial diversity and defects in gut brain axis are linked to AD. Probiotics are known to be one of the best preventative measures against cognitive decline in AD. Numerous in vivo trials and recent clinical trials have proven the effectiveness of selected bacterial strains in slowing down the progression of AD. It is proven that probiotics modulate the inflammatory process, counteract with oxidative stress, and modify gut microbiota. Thus, this review summarizes the current evidence, diversity of bacterial strains, defects of gut brain axis in AD, harmful bacterial for AD, and the mechanism of action of probiotics in preventing AD. A literature search on selected databases such as PubMed, Semantic Scholar, Nature, and Springer link have identified potentially relevant articles to this topic. However, upon consideration of inclusion criteria and the limitation of publication year, only 22 articles have been selected to be further reviewed. The search query includes few sets of keywords as follows. (1) Probiotics OR gut microbiome OR microbes AND (2) Alzheimer OR cognitive OR aging OR dementia AND (3) clinical trial OR in vivo OR animal study. The results evidenced in this study help to clearly illustrate the relationship between probiotic supplementation and AD. Thus, this systematic review will help identify novel therapeutic strategies in the future as probiotics are free from triggering any adverse effects in human body.
    Matched MeSH terms: Probiotics/administration & dosage*
  15. Mohd Isa D, Shahar S, He FJ, Majid HA
    Nutrients, 2021 Dec 17;13(12).
    PMID: 34960086 DOI: 10.3390/nu13124534
    Health literacy has been recognized as a significant social determinant of health, defined as the ability to access, understand, appraise, and apply health-related information across healthcare, disease prevention, and health promotion. This systematic review aims to understand the relationship between health literacy, blood pressure, and dietary salt intake. A web-based search of PubMed, Web of Science, CINAHL, ProQuest, Scopus, Cochrane Library, and Prospero was performed using specified search/MESH terms and keywords. Two reviewers independently performed the data extraction and analysis, cross-checked, reviewed, and resolved any discrepancies by the third reviewer. Twenty out of twenty-two studies met the inclusion criteria and were rated as good quality papers and used in the final analysis. Higher health literacy had shown to have better blood pressure or hypertension knowledge. However, the relationship between health literacy with dietary salt intake has shown mixed and inconsistent findings. Studies looking into the main four domains of health literacy are still limited. More research exploring the links between health literacy, blood pressure, and dietary salt intake in the community is warranted. Using appropriate and consistent health literacy tools to evaluate the effectiveness of salt reduction as health promotion programs is required.
    Matched MeSH terms: Sodium Chloride, Dietary/administration & dosage*
  16. Nwanaji-Enwerem JC, Chung FF, Van der Laan L, Novoloaca A, Cuenin C, Johansson H, et al.
    Clin Epigenetics, 2021 12 17;13(1):224.
    PMID: 34920739 DOI: 10.1186/s13148-021-01218-y
    Metformin and weight loss relationships with epigenetic age measures-biological aging biomarkers-remain understudied. We performed a post-hoc analysis of a randomized controlled trial among overweight/obese breast cancer survivors (N = 192) assigned to metformin, placebo, weight loss with metformin, or weight loss with placebo interventions for 6 months. Epigenetic age was correlated with chronological age (r = 0.20-0.86; P 
    Matched MeSH terms: Metformin/administration & dosage
  17. Khor CS, Tsuji R, Lee HY, Nor'e SS, Sahimin N, Azman AS, et al.
    Nutrients, 2021 Dec 16;13(12).
    PMID: 34960061 DOI: 10.3390/nu13124507
    Dengue fever (DF) is a mosquito-borne disease still with no effective treatment or vaccine available. A randomized, placebo-controlled, double-blinded, parallel-group trial was undertaken to evaluate the efficacy of oral intake of Lactococcus lactis strain plasma (LC-Plasma) on the presentation and severity of DF-like symptoms among healthy volunteers. Study participants (320) were assigned into two groups, and consumed either placebo or LC-Plasma tablets (approximately 100 billion cells/day) for 8 weeks. The clinical symptoms of DF were self-recorded through questionnaires, and exposure to DENV was determined by serum antibody and/or DENV antigen tests. No significant differences between groups were observed for exposure to DENV, or the symptomatic ratio. Results obtained showed that participants from the LC-Plasma group reported a significant reduction in the cumulative incidence days of DF-like symptoms, which include fever (p < 0.001), muscle pain (p < 0.005), joint pain (p < 0.001), and pain behind the eyes (p < 0.001), compared to that of the placebo group. Subgroup analysis revealed a significantly (p < 0.05) reduced severity score in the LC-Plasma group when study sites were separately analyzed. Overall, our findings suggest that LC-Plasma supplementation reduces the cumulative days with DF-like symptoms, and the severity of the symptoms. Daily oral intake of LC-Plasma, hence, is shown to mitigate the DF-like symptoms.
    Matched MeSH terms: Probiotics/administration & dosage*
  18. Lalani S, Tan SH, Tan KO, Lim HX, Ong KC, Wong KT, et al.
    Life Sci, 2021 Dec 15;287:120097.
    PMID: 34715144 DOI: 10.1016/j.lfs.2021.120097
    AIMS: Enterovirus A71 (EV-A71) is an etiological agent of hand foot and mouth disease (HFMD) and has the potential to cause severe neurological infections in children. L-SP40 peptide was previously known to inhibit EV-A71 by prophylactic action. This study aimed to identify the mechanism of inhibition in Rhabdomyosarcoma (RD) cells and in vivo therapeutic potential of L-SP40 peptide in a murine model.

    MAIN METHODS: A pull-down assay was performed to identify the binding partner of the L-SP40 peptide. Co-immunoprecipitation and co-localization assays with the L-SP40 peptide were employed to confirm the receptor partner in RD cells. The outcomes were validated using receptor knockdown and antibody blocking assays. The L-SP40 peptide was further evaluated for the protection of neonatal mice against lethal challenge by mouse-adapted EV-A71.

    KEY FINDINGS: The L-SP40 peptide was found to interact and co-localize with nucleolin, the key attachment receptor of Enteroviruses A species, as demonstrated in the pull-down, co-immunoprecipitation and co-localization assays. Knockdown of nucleolin from RD cells led to a significant reduction of 3.5 logs of viral titer of EV-A71. The L-SP40 peptide demonstrated 80% protection of neonatal mice against lethal challenge by the mouse-adapted virus with a drastic reduction in the viral loads in the blood (~4.5 logs), skeletal muscles (1.5 logs) and brain stem (1.5 logs).

    SIGNIFICANCE: L-SP40 peptide prevented severe hind limb paralysis and death in suckling mice and could serve as a potential broad-spectrum antiviral candidate to be further evaluated for safety and potency in future clinical trials against EV-A71.

    Matched MeSH terms: Peptide Fragments/administration & dosage
  19. Vyas T, Rapalli VK, Chellappan DK, Dua K, Dubey SK, Singhvi G
    Life Sci, 2021 Dec 15;287:120148.
    PMID: 34785190 DOI: 10.1016/j.lfs.2021.120148
    BACKGROUND: Biofilms are microcolonies of microbes that form communities with a variety of microbes, exhibit the same gene composition but differ in gene expression. Biofilm-associated infections have been in existence for a long, however, biofilm-associated skin disorders have not been investigated much.

    OBJECTIVES: Biofilms, which are made mostly of the matrix can be thought of as communities of microbes that are more virulent and more difficult to eradicate as compared to their planktonic counterparts. Currently, several formulations are available in the market which have the potential to treat biofilm-assisted skin disorders. However, the existing pharmacotherapies are not competent enough to cure them effectively and entirely, in several cases.

    KEY FINDINGS: Especially with the rising resistance towards antibiotics, it has become particularly challenging to ameliorate these disorders completely. The new approaches are being used to combat biofilm-associated skin disorders, some of them being photodynamic therapy, nanotherapies, and the use of novel drug delivery systems. The focus of attention, however, is nanotherapy. Micelles, solid lipid nanoparticles, quatsomes, and many others are being considered to find a better solution for the biofilm-associated skin disorders.

    SIGNIFICANCE: This review is an attempt to give a perspective on these new approaches for treating bacterial biofilms associated with skin disorders.

    Matched MeSH terms: Anti-Bacterial Agents/administration & dosage*
  20. Keane A, Ng CW, Simms KT, Nguyen D, Woo YL, Saville M, et al.
    Int J Cancer, 2021 12 15;149(12):1997-2009.
    PMID: 34363620 DOI: 10.1002/ijc.33759
    The WHO has launched a global strategy to eliminate cervical cancer through the scale-up of human papillomavirus (HPV) vaccination, cervical screening, and cervical cancer treatment. Malaysia has achieved high-coverage HPV vaccination since 2010, but coverage of the existing cytology-based program remains low. Pilot studies found HPV self-sampling was acceptable and effective, with high follow-up rates when a digital registry was used, and recently the Malaysian Government announced plans for a national HPV-based screening program. We therefore evaluated the impact of primary HPV screening with self-collection in Malaysia in the context of Malaysia's existing vaccination program. We used the "Policy1-Cervix" modeling platform to assess health outcomes, cost-effectiveness, resource use and cervical cancer elimination timing (the year when cervical cancer rates reach four cases per 100 000 women) of implementing primary HPV testing with self-collection, assuming 70% routine-screening coverage could be achieved. Based on available data, we assumed that compliance with follow-up was 90% when a digital registry was used, but that compliance with follow-up would be 50-75% without the use of a digital registry. We found that the current vaccination program would prevent 27 000 to 32 200 cervical cancer cases and 11 700 to 14 000 deaths by 2070. HPV testing with a digital registry was cost-effective (CER = $US 6953-7549 
    Matched MeSH terms: Papillomavirus Vaccines/administration & dosage
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